Preexisting Serum Autoantibodies Against the NMDAR Subunit NR1 Modulate Evolution of Lesion Size in Acute Ischemic Stroke.
Stroke
; 46(5): 1180-6, 2015 May.
Article
em En
| MEDLINE
| ID: mdl-25765725
ABSTRACT
BACKGROUND AND PURPOSE:
Recently, we reported high seroprevalence (age-dependent up to >19%) of N-methyl-d-aspartate-receptor subunit NR1 (NMDAR1) autoantibodies in both healthy and neuropsychiatrically ill subjects (N=4236). Neuropsychiatric syndrome relevance was restricted to individuals with compromised blood-brain barrier, for example, apolipoprotein E4 (APOE4) carrier status, both clinically and experimentally. We now hypothesized that these autoantibodies may upon stroke be protective in individuals with hitherto intact blood-brain barrier, but harmful for subjects with chronically compromised blood-brain barrier.METHODS:
Of 464 patients admitted with acute ischemic stroke in the middle cerebral artery territory, blood for NMDAR1 autoantibody measurements and APOE4 carrier status as indicator of a preexisting leaky blood-brain barrier was collected within 3 to 5 hours after stroke. Evolution of lesion size (delta day 7-1) in diffusion-weighted magnetic resonance imaging was primary outcome parameter. In subgroups, NMDAR1 autoantibody measurements were repeated on days 2 and 7.RESULTS:
Of all 464 patients, 21.6% were NMDAR1 autoantibody-positive (immunoglobulin M, A, or G) and 21% were APOE4 carriers. Patients with magnetic resonance imaging data available on days 1 and 7 (N=384) were divided into 4 groups according to NMDAR1 autoantibody and APOE4 status. Groups were comparable in all stroke-relevant presenting characteristics. The autoantibody+/APOE4- group had a smaller mean delta lesion size compared with the autoantibody-/APOE4- group, suggesting a protective effect of circulating NMDAR1 autoantibodies. In contrast, the autoantibody+/APOE4+ group had the largest mean delta lesion area. NMDAR1 autoantibody serum titers dropped on day 2 and remounted by day 7.CONCLUSIONS:
Dependent on blood-brain barrier integrity before an acute ischemic brain injury, preexisting NMDAR1 autoantibodies seem to be beneficial or detrimental.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Autoanticorpos
/
Isquemia Encefálica
/
Receptores de N-Metil-D-Aspartato
/
Acidente Vascular Cerebral
Tipo de estudo:
Etiology_studies
/
Observational_studies
Limite:
Aged
/
Aged80
/
Female
/
Humans
/
Male
/
Middle aged
Idioma:
En
Revista:
Stroke
Ano de publicação:
2015
Tipo de documento:
Article